Background Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims.The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats.Then besides the sham operation group,the SCI rats were randomly divided into four groups:natural healing group,gene therapy group,rehabilitation training group,and combination therapy group (gene therapy in combination with rehabilitation training).Motor dysfunction,protein expression of GDNF,edema formation,and cell injury were examined 7,14,and 21 days after trauma.Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF,especially after the 14th day,and could protect the motor neuron ceils.Early rehabilitative treatment resulted in significantly improved motor function,reduced edema formation,and protected the cells from injury,especially after the 7th and 14th days,and increased the GDNF expression in the damaged area,which was most evident after Day 14.The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

BACKGROUND:Establishing a chondrocyte model of osteoarthritis is of great significance for further explaining the pathological process of osteoarthritis and evaluating and screening the therapeutic drugs of osteoarthritis. OBJECTIVE:To evaluate the effect of interleukin-1β to induce osteoarthritis models in rat chondrocyte models,thereby providing a reference for further exploration of drug treatment of osteoarthritis. METHODS:Chondrocytes were isolated from the hip cartilage of 3-week-old Sprague-Dawley rats by mechanical shearing and enzymatic digestion,and then identified.Chondrocytes were randomly divided into three groups:control group,5 ng/mL interleukin-1β-induced group,10 ng/mL interleukin-1β-induced group,with induction times of 24 and 48 hours.Chondrocyte proliferation activity was detected by MTT.Real-Time PCR was used to detect the expression of type Ⅱ collagen,Aggrecan,sex-determining region Y-box protein 9(Sox9),matrix metalloproteinase 13,and a disintegrin and metaloproteinase with thrombospondin-like motifs-5(Adamts5)mRNA.Western blot was used to detect the expression of type Ⅱ collagen,Sox9,matrix metalloproteinase 13 and Adamts5. RESULTS AND CONCLUSION:Primary rat chondrocytes were successfully isolated and cultured.Induction of chondrocytes by interleukin-1β at 10 ng/mL for 24 hours could significantly reduce cell proliferation and viability(P＜0.05),while the 5 ng/mL interleukin-1β-induced group required 48 hours of induction to cause a significant decrease in cell proliferation and viability.Real-Time PCR results showed that compared with the control group,5 or 10 ng/mL interleukin-1β induction for 24 and 48 hours significantly reduced the expression levels of type Ⅱ collagen,Aggrecan,Sox9 mRNAs(P＜0.05)and increased the expression levels of matrix metalloproteinase 13 and Adamts5 mRNAs(P＜0.05).Compared with the 10 ng/mL interleukin-1β-induced group,5 ng/mL interleukin-1β induction significantly increased the mRNA expression of matrix metalloproteinase 13 and Adamts5 in chondrocytes after 48 hours of induction(P＜0.05).Western blot results showed that compared with the control group,10 ng/mL interleukin-1β induction for 24 hours and 5 ng/mL interleukin-1β induction for 48 hours significantly decreased the protein expression of type Ⅱ collagen and Sox9 in chondrocytes(P＜0.05),and significantly increased the protein expression of matrix metalloproteinase 13 and Adamts5(P＜0.05).To conclude,compared with 5 ng/mL interleukin-1β,10 ng/mL interleukin-1β may have more obvious effects on chondrocytes for 24 hours,while 5 and 10 ng/mL interleukin-1β have similar effects after 48 hours of intervention.

ObjectiveTo analyze the disease and functioning characteristics of older adults with sarcopenia, the main exercise rehabilitation interventions, and its health benefits. MethodsLiterature related to exercise rehabilitation for older adults with sarcopenia was searched in PubMed, Medline, Embase, Cochrane Library and CNKI, from 2013 to 2023. The quality of included systematic reviews were evaluated. ICD-11 and ICF classification systems, and PICO framework from PRISMA guideline were used to report characteristics of the disease and functioning of the population, the exercise rehabilitation interventions, and its health benefits. ResultsFinally, seven systematic reviews from Netherlands, Spain, China, Brazil and Mexico were included, covering 98 related randomized controlled trials, involving 19 794 participants. These systematic reviews mainly came from the journals in the fields of aging, rehabilitation, nutrition, public health and physical exercise, and were published between 2018 and 2023. Exercise rehabilitation for sarcopenia were categorized into three types: exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Interventions primarily included aerobic training, resistance training, gait training, strength training, and balance and flexibility exercises. The intervention frequency was six to 150 minutes, one to five times a week, with intensities ranging from low to high, over a duration of six to 144 weeks. The health benefits for older adults with sarcopenia from exercise rehabilitation were reflected in improvement in physical function and structure, and enhancement in activity and participation. In terms of body function and structure, exercise rehabilitation improved muscle strength, control, coordination, gait, balance, leg extension, leg press, back strength and grip strength, and increased muscle quality. In terms of activity and participation, exercise rehabilitation improved physical activity performance, such as walking speed and time of five-repetition chair stand test. ConclusionExercise rehabilitation for sarcopenia includes exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Exercise rehabilitation can improve the physical function and structure, and enhance activity and participation.

BACKGROUNDSpinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.

METHODSSCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma.

RESULTSThe topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.

CONCLUSIONThese observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

Animals ; Cell Line ; Dependovirus ; genetics ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; physiology ; Humans ; Immunohistochemistry ; Male ; Motor Activity ; genetics ; physiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism